The present invention relates to a method of alleviating or preventing a migraine headache through the administration of a mast cell degranulation blocking agent.
A) Migraines
Migraine headaches are known to produce the most intense headache reported, which are comparable to that of a brain aneurysm rupture. As many as 15% of all people, especially in industrialized societies, are sufferers, with an estimated yearly cost due to treatment and work lost in the United States of America alone of almost one billion dollars. Prior to the present invention, there has been no effective way to prevent the last minute onset of the migraine headache.
The pathophysiology of migraine headaches involves vasoconstriction (the closing or tightening of arteries, which reduces blood flow) and vasodilation (the opening of the vessels to increase blood flow). It appears that a variety of stimuli, such as intense light, noise, anxiety, exertion, cold, heat, hormones, food additives and certain foods, result in constriction of extracranial vessels. The vasoconstriction is followed by a sequential or reflex powerful vasodilation, which subsequently spreads to intracranial vessels. It is during this phase that a patient feels an intense, throbbing headache. Increased levels of norepinephrine, serotonin, bradykinin and substance P, as well as products of tissue anoxia are considered to be the endogenous pain producing molecules accompanied by direct sensory nerve stimulation, because of stretching due to vasoconstriction and vasodilation.
The phases of a migraine headache have been separated into the prodrome, aura and acute painful headache stages. The prodrome is the primary stage of a migraine attack characterized by an alteration of mood, energy or passive functions. This stage can occur for hours before the onset of the headache. The mood alterations include euphoria, loquaciousness, unprovoked apathy, depression, inertia, drowsiness, irritability, repetitive yawning, aggression and heightened sensitivity to various levels of sound (sonophobia). Nausea and vomiting, as well as paresthesias in the extremities, may also accompany these symptoms.
The aura or second stage has been defined by the onset of fear of light (photophobia) and visual disturbances brought on by a reduction of cerebral blood flow due to vasospasm.
The headache phase is vascular with distension and increased pulsation of cranial arteries. Increased vascular permeability is associated with the release of peptides, especially bradykinin and substance P, as well as molecules such as histamine and serotonin, which cause local pain when they reach perivascular nerve endings.
Migraine headaches develop suddenly, and reach maximal intensity very quickly, in contrast to ordinary muscular headaches, which develop gradually and rarely, if ever, reach a severity comparable to that of migraine headaches. Patients suffering from migraine headaches are often so well aware of the pain that will ensue from an impending migraine that they become apprehensive and frightened. As a result of this anxiety, the patients hyperventilate and/or tense their neck muscles. Both of these effects usually lead to a muscle tension headache. In other words, the mere anticipation and fear of an impending migraine headache brings about an ordinary muscular headache in virtually all migraine patients. The patients can thus suffer from two different types of affliction simultaneously.